An Efficient Iodine-Catalyzed
Benzylation Reaction of 1,3-Dicarbonyl Compounds

Zhongxian Li; Zheng Duan; Huaiqiu Wang; Rongqiang Tian; Qianrui Zhu; Yangjie Wu

doi:10.1055/s-2008-1078216

LETTER

An Efficient Iodine-Catalyzed Benzylation Reaction of 1,3-Dicarbonyl Compounds

Zhongxian Li, Zheng Duan*, Huaiqiu Wang, Rongqiang Tian, Qianrui Zhu, Yangjie Wu*
Chemistry Department, The Key Lab of Chemical Biology and Organic Chemistry of Henan Province, The Key and Open Lab of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, P. R. of China
Fax: +86(371)67979408; e-Mail: duanzheng@zzu.edu.cn; e-Mail: wyj@zzu.edu.cn;

Abstract

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Abstract

Under mild conditions, iodine promotes the direct alkylation of 1,3-dicarbonyl compounds with benzylic alcohols or benzylic acetates.

Key words

iodine - catalysis - benzylation - Friedel-Crafts - C-H activation

Volltext

Referenzen

References and Notes

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For Bi-catalyzed, see:

<A NAME="RW07808ST-8A">8a</A> Rueping M. Nachtsheim BJ. Ieawsuwan W. Adv. Synth. Catal. 2006, 348: 1033

<A NAME="RW07808ST-8B">8b</A> Rueping M. Nachtsheim BJ. Kuenkel A. Org. Lett. 2007, 9: 825

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<A NAME="RW07808ST-10A">10a</A> Sanz R. Miguel D. Martinez A. Alvarez-Gutierrez JM. Rodriguez F. Org. Lett. 2007, 9: 2027

<A NAME="RW07808ST-10B">10b</A> Sanz R. Miguel D. Martinez A. Alvarez-Gutierrez JM. Rodriguez F. Org. Lett. 2007, 9: 727

<A NAME="RW07808ST-11A">11a</A> Deka N. Kalita DJ. Borah R. Sarma JC. J. Org. Chem. 1997, 62: 1563

<A NAME="RW07808ST-11B">11b</A> Firouzabadi H. Iranpoor N. Hazarkhani H. J. Org. Chem. 2001, 66: 7527

<A NAME="RW07808ST-11C">11c</A> Chu C.-M. Huang W.-J. Liu J.-T. Yao C.-F. Tetrahedron Lett. 2007, 48: 6881 ; and references cited therein

General Procedure
All procedures were carried out under air. To a 10 mL flask, benzylic alcohols or benzylic acetates (0.5 mmol), 1,3-dicarbonyl compounds, MeNO₂ (2 mL), and molecular iodine (13 mg, 0.05 mmol) were added successively. The mixture was magnetically stirred at 80 ˚C. After completion of the reaction (by GC), the solvent was concentrated under reduced pressure by an aspirator, and the residue was purified by preparative TLC using PE-EtOAc (10:1) as an eluent to afford products.

Selected Spectroscopic Data All prepared compounds were known and identified by ^¹H NMR, ^¹³C NMR, and MS.
Compound 3a: ^¹H NMR (400 MHz, CDCl₃): δ = 7.31-7.27 (m, 2 H), 7.22-7.18 (m, 3 H), 4.04 (d, J = 11.3 Hz, 1 H), 3.63-3.55 (m, 1 H), 2.56 (s, 3 H), 1.83 (s, 3 H), 1.21 (d, J = 6.9 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.5, 203.4, 143.0, 128.8, 127.3, 127.0, 76.7, 40.4, 29.8, 29.7, 20.8. ESI-MS: m/z = 227.0 [M + Na⁺].
Compound 3b: ^¹H NMR (400 MHz, CDCl₃): δ = 7.28-7.25 (m, 2 H), 7.15-7.12 (m, 2 H), 4.00 (d, J = 11.3 Hz, 1 H), 3.61-3.57 (m, 1 H), 2.26 (s, 3 H), 1.87 (s, 3 H), 1.19 (d, J = 6.9 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.0, 202.9, 141.5, 132.6, 128.9, 128.6, 76.5, 39.6, 29.8, 29.6, 20.7. ESI-MS: m/z = 261.1 [M + Na⁺].
Compound 3c: ^¹H NMR (400 MHz, CDCl₃): δ = 7.12-7.08 (m, 2 H), 6.84-6.82 (m, 2 H), 3.98 (d, J = 11.3 Hz, 1 H), 3.78 (s, 3 H), 3.57-3.53 (m, 1 H), 2.26 (s, 3 H), 1.84 (s, 3 H), 1.18 (d, J = 6.9 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.6, 203.5, 158.4, 134.9, 128.2, 114.1, 76.9, 55.1, 39.7, 29.8, 29.6, 20.9. ESI-MS: m/z = 257.0 [M + Na⁺].
Compound 3d: ^¹H NMR (400 MHz, CDCl₃): δ = 7.22-7.18 (m, 2 H), 7.14-7.12 (m, 1 H), 6.97 (d, J = 7.8 Hz, 2 H), 6.88 (s, 1 H), 6.69 (s, 1 H), 5.48 (d, J = 11.7 Hz, 1 H), 4.94 (d, J = 11.7 Hz, 1 H), 2.55 (s, 3 H), 2.29 (s, 3 H), 2.20 (s, 3 H), 1.99 (s, 3 H), 1.83 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.7, 203.0, 141.1, 137.3, 136.7, 136.7, 134.9, 131.3, 129.6, 128.4, 126.9, 126.1, 70.5, 43.0, 30.3, 28.9, 21.7, 20.9, 20.7. Anal. Calcd for: C, 81.78; H, 7.84. Found: C, 81.74; H, 7.93.
Compound 3e: ^¹H NMR (400 MHz, CDCl₃): δ = 7.22-7.18 (m, 2 H), 7.14-7.11 (m, 1 H), 6.94 (d, J = 7.9 Hz, 2 H), 6.88 (s, 1 H), 5.67 (d, J = 11.3 Hz, 1 H), 4.94 (d, J = 11.3 Hz, 1 H), 2.46 (s, 3 H), 2.34 (s, 3 H), 2.28 (s, 3 H), 2.08 (s, 3 H), 1.88 (s, 3 H), 1.72 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.8, 202.8, 142.0, 137.9, 135.3, 134.1, 133.8, 133.1, 131.3, 128.5, 126.8, 126.0, 71.9, 43.3, 29.8, 29.2, 21.5, 20.4, 17.1, 16.8. Anal. Calcd for: C, 81.95; H, 8.13. Found: C, 81.64; H, 8.37.
Compound 3f: ^¹H NMR (400 MHz, CDCl₃): δ = 7.32 (d, J = 8.4 Hz, 2 H), 6.88 (s, 1 H), 6.84 (d, J = 8.3 Hz, 2 H), 6.71 (s, 1 H), 5.40 (d, J = 11.6 Hz, 1 H), 4.89 (d, J = 11.6 Hz, 1 H), 2.53 (s, 3 H), 2.29 (s, 3 H), 2.21 (s, 3 H), 1.98 (s, 3 H), 1.83 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.3, 202.6, 140.4, 137.3, 137.0, 136.6, 134.4, 131.5 (2C), 129.8, 128.8, 120.0, 70.4, 42.5, 30.3, 29.0, 21.7, 21.0, 20.7. Anal. Calcd for: C, 65.12; H, 5.99. Found: C, 65.03; H, 6.04.
Compound 3g: ^¹H NMR (400 MHz, CDCl₃): δ = 7.01 (d, J = 8.0 Hz, 2 H), 6.87-6.85 (m, 3 H), 6.69 (s, 1 H), 5.42 (d, J = 11.7 Hz, 1 H), 4.92 (d, J = 11.7 Hz, 1 H), 2.55 (s, 3 H), 2.29 (s, 3 H), 2.26 (s, 3 H), 2.21 (s, 3 H), 2.01 (s, 3 H), 1.82 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 204.0, 203.2, 138.1, 137.3, 136.8, 136.7, 135.7, 135.1, 131.4, 129.7, 129.1, 126.9, 70.8, 42.9, 30.2, 28.9, 21.8, 21.0, 20.9, 20.8. ESI-MS: m/z = 345.2 [M + Na⁺].
Compound 3h: ^¹H NMR (400 MHz, CDCl₃): δ = 4.19 (s, 5 H), 4.16-4.05 (m, 4 H), 3.59 (d, J = 9.7 Hz, 1 H), 3.29-3.25 (m, 1 H), 2.15 (s, 3 H), 1.87 (s, 3 H), 1.26 (d, J = 6.5 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 204.5, 203.4, 91.7, 77.3, 68.8, 68.7, 67.8, 67.6, 65.4, 34.6, 32.0, 29.4, 18.3. Anal. Calcd for: C, 65.40; H, 6.46. Found: C, 65.40; H, 6.54.
Compound 3i: ^¹H NMR (400 MHz, CDCl₃): δ = 7.50 (s, 1 H), 7.40 (s, 5 H), 2.43 (s, 3 H), 2.29 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 205.7, 196.6, 142.7, 139.9, 132.8, 130.7, 129.7, 129.0, 31.7, 26.5. ESI-MS: m/z = 211.0 [M + Na⁺].
Compound 3k: ^¹H NMR (400 MHz, CDCl₃): δ = 8.10-8.08 (m, 1 H), 7.49-7.04 (m, 9 H), 4.94 (d, J = 10.9 Hz, 1 H), 3.90-3.86 (m, 1 H), 1.90 (s, 3 H), 1.21 (d, J = 6.8 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.1, 195.2, 143.2, 137.2, 133.9, 128.9, 128.8, 128.5, 127.5, 127.0, 70.8, 41.0, 28.0, 21.6.
Another diastereomer: ^¹H NMR (400 MHz, CDCl₃): δ = 7.80-7.78 (m, 1 H), 7.49-7.04 (m, 9 H), 4.50 (d, J = 11.0 Hz, 1 H), 3.90-3.86 (m, 1 H), 2.23 (s, 3 H), 1.30 (d, J = 7.0 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 203.6, 195.2, 143.5, 137.0, 133.4, 128.9, 128.6, 128.5, 127.4, 126.6, 71.4, 40.4, 27.6, 20.3.
Compound 3l: ^¹H NMR (400 MHz, CDCl₃): δ = 8.05-8.02 (m, 2 H), 7.74 (d, J = 7.4 Hz, 2 H), 7.57-7.53 (m, 1 H), 7.46-7.39 (m, 3 H), 7.29-7.25 (m, 4 H), 7.19-7.15 (m, 2 H), 7.09-7.05 (m, 1 H), 5.61 (d, J = 10.1 Hz, 1 H), 4.10-4.06 (m, 1 H), 1.34 (d, J = 7.0 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 195.0, 194.6, 143.8, 137.2, 136.9, 133.6, 133.0, 128.9, 128.8, 128.5, 128.5, 128.4, 127.7, 126.6, 64.9, 41.2, 20.2. ESI-MS: m/z = 351.3 [M + Na⁺].
Compound 3m: ^¹H NMR (400 MHz, CDCl₃): δ = 7.27-7.20 (m, 3 H), 7.14-7.12 (m, 2 H), 3.79 (q, J = 7.0 Hz, 1 H), 2.53-2.46 (m, 2 H), 2.19-2.10 (m, 1 H), 1.97-1.92 (m, 1 H), 1.86 (s, 3 H), 1.84-1.79 (m, 2 H), 1.67-1.55 (m, 2 H), 1.30 (d, J = 7.1 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 208.6, 205.9, 141.4, 128.7, 128.3, 127.0, 72.1, 42.7, 42.4, 28.2, 26.7, 25.9, 22.2, 17.4. ESI-MS: m/z = 267.1 [M + Na⁺].
Another diastereomer: ^¹H NMR (400 MHz, CDCl₃): δ = 7.28-7.24 (m, 4 H), 7.21-7.19 (m, 1 H), 3.89 (q, J = 7.4 Hz, 1 H), 2.38-2.34 (m, 2 H), 2.16-2.07 (m, 1 H), 2.12 (s, 3 H), 1.67-1.65 (m, 1 H), 1.63-1.60 (m, 1 H), 1.47-1.43 (m, 1 H), 1.42-1.40 (m, 2 H), 1.16 (d, J = 7.4 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 209.2, 205.4, 141.9, 129.9, 127.8, 126.7, 72.1, 42.3, 41.5, 29.4, 27.1, 25.5, 21.9, 16.2. ESI-MS: m/z = 267.1 [M + Na⁺].
Compound 3n: ^¹H NMR (400 MHz, CDCl₃): δ = 7.30-7.26 (m, 2 H), 7.23-7.7.19 (m, 3 H), 3.87 (q, J = 7.1 Hz, 2 H), 3.81-3.73 (m, 1 H), 3.57-3.52 (m, 1 H), 1.93 (s, 3 H), 1.23 (d, J = 6.9 Hz, 3 H), 0.94 (t, J = 7.2 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 202.4, 168.6, 143.1, 128.7, 127.4, 126.9, 67.0, 61.5, 40.1, 29.9, 20.6, 14.1. ESI-MS: m/z = 257.1 [M + Na⁺].
Another diastereomer: ^¹H NMR (400 MHz, CDCl₃): δ = 7.30-7.26 (m, 2 H), 7.23-7.7.19 (m, 3 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.81-3.73 (m, 1 H), 3.57-3.52 (m, 1 H), 2.30 (s, 3 H), 1.30 (d, J = 6.9 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 202.4, 168.2, 143.3, 128.4, 127.5, 126.8, 67.6, 61.1, 39.8, 29.5, 20.4, 13.7. ESI-MS: m/z = 257.1 [M + Na⁺].
Compound 3o: ^¹H NMR (400 MHz, CDCl₃): δ = 7.35-7.32 (m, 2 H), 7.28-7.25 (m, 3 H), 5.27 (s, 1 H), 5.22-5.18 (q, J = 6.4 Hz, 1 H), 2.47-2.43 (m, 2 H), 2.30-2.26 (m, 2 H), 1.98-1.90 (m, 2 H), 1.57 (d, J = 6.4 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 199.7, 176.5, 141.3, 128.8, 128.0, 125.3, 104.6, 76.6, 36.6, 29.3, 23.6, 21.1.
Compound 5a: ^¹H NMR (400 MHz, CDCl₃): δ = 7.26-7.21 (m, 2 H), 7.17-7.12 (m, 3 H), 6.81 (s, 2 H), 4.63 (q, J = 7.3 Hz, 1 H), 2.25 (s, 3 H), 2.10 (s, 6 H), 1.64 (d, J = 7.3 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 145.5, 140.1, 136.6, 135.4, 130.0, 128.2, 126.9, 125.3, 37.9, 21.1, 20.8, 16.9.
Compound 5b: ^¹H NMR (400 MHz, CDCl₃): δ = 7.28-7.21 (m, 4 H), 7.17-7.14 (m, 1 H), 5.83 (s, 1 H), 3.89 (q, J = 7.2 Hz, 1 H), 2.20 (s, 3 H), 2.14 (s, 3 H), 1.50 (d, J = 7.3 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 149.2, 146.6, 144.7, 128.4, 127.1, 125.9, 124.1, 106.0, 35.6, 22.1, 13.6, 11.7.
Compound 5c: ^¹H NMR (400 MHz, CDCl₃): δ = 7.27-7.23 (m, 2 H), 7.19-7.12 (m, 3 H), 6.50 (s, 1 H), 4.08 (q, J = 7.2 Hz, 1 H), 2.35 (s, 3 H), 2.25 (s, 3 H), 1.54 (d, J = 7.2 Hz, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 146.3, 141.5, 135.1, 130.2, 128.4, 127.3, 125.9, 125.3, 38.3, 22.1, 15.4, 13.0. ESI-MS: m/z = 239.4 [M + Na⁺].

<A NAME="RW07808ST-14">14</A> During the preparation of this manuscript, a similar result was reported, see: Srihari P. Bhunia DC. Sreedhar P. Yadav JS. Synlett 2008, 1045

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